Parkinson's disease-associated human P5B-ATPase ATP13A2 increases spermidine uptake

Abstract

P-type ion pumps are membrane transporters that have been classified into five subfamilies termed P1–P5. The ion transported by the P5-ATPases is not known. Five genes, ATP13A (ATPase type 13A) 1–ATP13A5, that belong to the P5-ATPase group have been identified in humans. Mutations of the human gene ATP13A2 underlie a form of PD (Parkinson's disease). Previous studies have suggested a relation between polyamines and P5B-ATPases. We have recently shown that the cytotoxicity induced by the polyamine analogue paraquat (1,1′-dimethyl-4,4′-bipyridinium), which is an environmental agent related to PD development, was increased in ATP13A2-expressing CHO (Chinese-hamster ovary) cells. In the present study we showed that ATP13A2-expressing CHO cells exhibit a 2-fold higher accumulation of spermidine. Increasing concentrations of spermidine reduced the viability of CHO cells stably expressing ATP13A2. The higher levels of spermidine attained by the ATP13A2-expressing CHO cells were correlated with an increase in the ATP-dependent spermidine uptake in an isolated subcellular fraction containing lysosomes and late endosomes. The results of the present study support the idea that the human P5B-ATPase ATP13A2 is involved in polyamine uptake.